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Annals of Medicine Dec 2023Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges... (Review)
Review
Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges and brain parenchyma, as well as the spinal cord and meninges; Disability and mortality rates are high. In recent years, due to the increase of drug-resistant tuberculosis patients, population mobility and the prevalence of acquired immune deficiency syndrome, the incidence rate of tuberculosis has increased significantly, and tuberculous meningitis has also increased. At present, tuberculosis is still a worldwide infectious disease that seriously threatens human health, especially in underdeveloped and developing countries. China is the largest developing country in the world with a large population. The situation of tuberculosis prevention and control is grim. Its disability rate is the highest in tuberculosis infection. In addition to the common non-specific manifestations, tuberculous meningoencephalitis may also have rare manifestations of stroke, hearing loss and visual loss. Understanding and timely improvement of corresponding examinations and targeted treatment will help improve the prognosis of patients.
Topics: Humans; Tuberculosis, Meningeal; Mycobacterium tuberculosis; Brain; Meningoencephalitis; China
PubMed: 36598144
DOI: 10.1080/07853890.2022.2164348 -
Developmental Cell Apr 2023The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells....
The arachnoid barrier, a component of the blood-cerebrospinal fluid barrier (B-CSFB) in the meninges, is composed of epithelial-like, tight-junction-expressing cells. Unlike other central nervous system (CNS) barriers, its' developmental mechanisms and timing are largely unknown. Here, we show that mouse arachnoid barrier cell specification requires the repression of Wnt-β-catenin signaling and that constitutively active β-catenin can prevent its formation. We also show that the arachnoid barrier is functional prenatally and, in its absence, a small molecular weight tracer and the bacterium group B Streptococcus can cross into the CNS following peripheral injection. Acquisition of barrier properties prenatally coincides with the junctional localization of Claudin 11, and increased E-cadherin and maturation continues after birth, where postnatal expansion is marked by proliferation and re-organization of junctional domains. This work identifies fundamental mechanisms that drive arachnoid barrier formation, highlights arachnoid barrier fetal functions, and provides novel tools for future studies on CNS barrier development.
Topics: Mice; Animals; beta Catenin; Meninges; Arachnoid; Blood-Brain Barrier; Central Nervous System; Tight Junctions
PubMed: 36996816
DOI: 10.1016/j.devcel.2023.03.005 -
Neuromolecular Medicine Sep 2021Traditionally, the primary role of the meninges is thought to be structural, i.e., to act as a surrounding membrane that contains and cushions the brain with... (Review)
Review
Traditionally, the primary role of the meninges is thought to be structural, i.e., to act as a surrounding membrane that contains and cushions the brain with cerebrospinal fluid. During development, the meninges is formed by both mesenchymal and neural crest cells. There is now emerging evidence that subsets of undifferentiated stem cells might persist in the adult meninges. In this mini-review, we survey representative studies of brain-meningeal interactions and discuss the hypothesis that the meninges are not just protective membranes, but instead contain multiplex stem cell subsets that may contribute to central nervous system (CNS) homeostasis. Further investigations into meningeal multipotent cells may reveal a "hidden" target for promoting neurovascular remodeling and repair after CNS injury and disease.
Topics: Adapalene; Adult Stem Cells; Animals; Brain Ischemia; Central Nervous System; Central Nervous System Diseases; Glymphatic System; Homeostasis; Humans; Male; Meninges; Multipotent Stem Cells; Neural Crest; Neural Stem Cells; Rats; Rats, Sprague-Dawley; Regeneration
PubMed: 33893971
DOI: 10.1007/s12017-021-08663-1 -
Communications Biology Feb 2024Crosstalk between central nervous system (CNS) and systemic responses is important in many pathological conditions, including stroke, neurodegeneration, schizophrenia,... (Review)
Review
Crosstalk between central nervous system (CNS) and systemic responses is important in many pathological conditions, including stroke, neurodegeneration, schizophrenia, epilepsy, etc. Accumulating evidence suggest that signals for central-systemic crosstalk may utilize glymphatic and lymphatic pathways. The glymphatic system is functionally connected to the meningeal lymphatic system, and together these pathways may be involved in the distribution of soluble proteins and clearance of metabolites and waste products from the CNS. Lymphatic vessels in the dura and meninges transport cerebrospinal fluid, in part collected from the glymphatic system, to the cervical lymph nodes, where solutes coming from the brain (i.e., VEGFC, oligomeric α-syn, β-amyloid) might activate a systemic inflammatory response. There is also an element of time since the immune system is strongly regulated by circadian rhythms, and both glymphatic and lymphatic dynamics have been shown to change during the day and night. Understanding the mechanisms regulating the brain-cervical lymph node (CLN) signaling and how it might be affected by diurnal or circadian rhythms is fundamental to find specific targets and timing for therapeutic interventions.
Topics: Central Nervous System; Lymphatic Vessels; Brain; Lymphatic System; Meninges
PubMed: 38402351
DOI: 10.1038/s42003-024-05911-5 -
Cellular and Molecular Life Sciences :... Oct 2023Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune... (Review)
Review
Meningeal lymphatic vessels (MLVs) help maintain central nervous system (CNS) homeostasis via their ability to facilitate macromolecule waste clearance and neuroimmune trafficking. Although these vessels were overlooked for centuries, they have now been characterized in humans, non-human primates, and rodents. Recent studies in mice have explored the stereotyped growth and expansion of MLVs in dura mater, the various transcriptional, signaling, and environmental factors regulating their development and long-term maintenance, and the pathological changes these vessels undergo in injury, disease, or with aging. Key insights gained from these studies have also been leveraged to develop therapeutic approaches that help augment or restore MLV functions to improve brain health and cognition. Here, we review fundamental processes that control the development of peripheral lymphatic networks and how these might apply to the growth and expansion of MLVs in their unique meningeal environment. We also emphasize key findings in injury and disease models that may reveal additional insights into the plasticity of these vessels throughout the lifespan. Finally, we highlight unanswered questions and future areas of study that can further reveal the exciting therapeutic potential of meningeal lymphatics.
Topics: Mice; Animals; Lymphatic Vessels; Meninges; Central Nervous System; Lymphatic System; Models, Animal
PubMed: 37872442
DOI: 10.1007/s00018-023-04984-5 -
Cancer Control : Journal of the Moffitt... Jan 2017Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia. (Review)
Review
BACKGROUND
Leukemic and lymphomatous meningitis is a major presentation of primary or secondary central nervous system (CNS) involvement by aggressive lymphomas or acute leukemia.
METHODS
The medical literature and ongoing clinical trials were reviewed on the clinical presentation, diagnosis, prognosis, prevention, and treatment of leukemic and lymphomatous meningitis.
RESULTS
Treatment for secondary leukemic and lymphomatous meningitis remains unsatisfactory, and efforts should be made to prevent and treat subclinical disease. Intrathecal and systemic chemotherapy remain the main therapeutic approaches for this disease. Outcomes have improved in patients with primary CNS lymphoma and meningeal involvement.
CONCLUSIONS
Appropriate selection of patients at high risk for leukemic and lymphomatous meningitis is important so that preventive strategies can decrease the incidence of this complication of leukemia and lymphoma. Use of chemotherapy agents that cross the blood-brain barrier and the adoption of high-dose chemotherapy with autologous hematopoietic stem cell transplantation have increased the proportion of patients whose primary disease is cured.
Topics: Disease Management; Humans; Leukemia; Lymphoma; Meningitis; Prognosis
PubMed: 28178710
DOI: 10.1177/107327481702400105 -
Cell Reports Mar 2023Tuberculous meningitis (TBM) is the most severe and deadly manifestation of tuberculosis. Neurological complications are observed in up to 50% of patients affected....
Tuberculous meningitis (TBM) is the most severe and deadly manifestation of tuberculosis. Neurological complications are observed in up to 50% of patients affected. Here, attenuated Mycobacterium bovis are injected into the cerebellum of mice, and histopathological images and cultured colonies confirm successful brain infection. Then, whole-brain tissue is dissected for 10X Genomics single-cell sequencing, and we acquire 15 cell types. Transcriptional changes of inflammation processes are found in multiple cell types. Specifically, Stat1 and IRF1 are shown to mediate inflammation in macrophages and microglia. For neurons, decreased oxidative phosphorylation activity in neurons is observed, which corresponds to TBM clinical symptoms of neurodegeneration. Finally, ependymal cells present prominent transcriptional changes, and decreased FERM domain containing 4A (Frmd4a) may contribute to TBM clinical symptoms of hydrocephalus and neurodegeneration. This study shows a single-cell transcriptome of M. bovis infection in mice and improves the understanding of brain infection and neurological complications in TBM.
Topics: Animals; Mice; Tuberculosis, Meningeal; BCG Vaccine; Brain; Inflammation; Single-Cell Analysis; Mycobacterium tuberculosis
PubMed: 36862557
DOI: 10.1016/j.celrep.2023.112177 -
Cancer Treatment and Research... 2021No large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken.
BACKGROUND
No large-scale study evaluating the usefulness of tamoxifen after meningioma surgery has been undertaken.
METHODS
We processed the French Système National des Données de Santé (SNDS) database using an algorithm combining the type of surgical procedure and the International Classification of Diseases to retrieve cases of meningiomas operated between 2007 and 2017. Survival analyses were performed using a matched cohort study.
RESULTS
251 patients treated by tamoxifen were extracted from a nationwide population-based cohort of 28 924 patients operated on for a meningioma over a 10-year period. 94% were female and median age at meningioma first surgery was 57 years IQR[47-67]. Tamoxifen treatment median duration was 1.4 years IQR[0.4-3.2]. Tamoxifen treatment median cumulative given dose was 11.4 gs, IQR[3.6-24.9]. There was a strong positive correlation between treatment duration and cumulative dose (τ=0.81, p<0.001). 6% of the patient had to be reoperated for a meningioma recurrence and 26.3% had radiotherapy. OS rates at 5 and 10 years were: 92.3%, CI[90.3-94.3] and 81.3%, CI[75.2-88] respectively. These 251 patients were matched by gender, age at surgery and grade with the same number of subjects within the nationwide cohort. Nor overall (HR=1.46, CI[0.86- 2.49], p=0.163) or progression-free survival (HR=1.2, CI[0.89- 1.62], p=0.239) were significantly improved by the tamoxifen treatment.
CONCLUSION
Using this unique database, in the setting of breast cancer, we could not conclude on a favourable effect of tamoxifen to prevent recurrence after meningioma surgery or to increase meningioma-related survival even in case of prolonged treatment duration or high cumulative given dose.
Topics: Aged; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Databases, Factual; Dose-Response Relationship, Drug; Female; France; Humans; Male; Meningeal Neoplasms; Meninges; Meningioma; Middle Aged; Neoplasm Recurrence, Local; Progression-Free Survival; Retrospective Studies; Survival Analysis; Tamoxifen; Time Factors
PubMed: 33647870
DOI: 10.1016/j.ctarc.2021.100343 -
Developmental Biology Oct 2017The axons of developing neurons travel long distances along stereotyped pathways under the direction of extracellular cues sensed by the axonal growth cone. Guidance...
The axons of developing neurons travel long distances along stereotyped pathways under the direction of extracellular cues sensed by the axonal growth cone. Guidance cues are either secreted proteins that diffuse freely or bind the extracellular matrix, or membrane-anchored proteins. Different populations of axons express distinct sets of receptors for guidance cues, which results in differential responses to specific ligands. The full repertoire of axon guidance cues and receptors and the identity of the tissues producing these cues remain to be elucidated. The meninges are connective tissue layers enveloping the vertebrate brain and spinal cord that serve to protect the central nervous system (CNS). The meninges also instruct nervous system development by regulating the generation and migration of neural progenitors, but it has not been determined whether they help guide axons to their targets. Here, we investigate a possible role for the meninges in neuronal wiring. Using mouse neural tissue explants, we show that developing spinal cord meninges produce secreted attractive and repulsive cues that can guide multiple types of axons in vitro. We find that motor and sensory neurons, which project axons across the CNS-peripheral nervous system (PNS) boundary, are attracted by meninges. Conversely, axons of both ipsi- and contralaterally projecting dorsal spinal cord interneurons are repelled by meninges. The responses of these axonal populations to the meninges are consistent with their trajectories relative to meninges in vivo, suggesting that meningeal guidance factors contribute to nervous system wiring and control which axons are able to traverse the CNS-PNS boundary.
Topics: Animals; Axon Guidance; Axons; Cues; Interneurons; Meninges; Mice, Transgenic; Motor Neurons; Spinal Cord
PubMed: 28784295
DOI: 10.1016/j.ydbio.2017.08.005 -
STAR Protocols Mar 2023The highly vascularized meninges protect the surface of the central nervous system and contain a dense network of immune cells controlling neuroinfection and...
The highly vascularized meninges protect the surface of the central nervous system and contain a dense network of immune cells controlling neuroinfection and neuroinflammation. Here, we present techniques for the immunological and virological assessment of mouse dural meninges. We describe steps for immunophenotyping including meninges extraction and digestion, immunostaining, and flow cytometry. We then describe viral assessment upon lymphocytic choriomeningitis virus infection including steps for fixation of the meninges in the skull, whole-mount immunohistochemistry, and confocal imaging. For complete details on the use and execution of this protocol, please refer to Rebejac et al. (2022)..
Topics: Animals; Mice; Flow Cytometry; Immunohistochemistry; Central Nervous System; Meninges; Head
PubMed: 36853673
DOI: 10.1016/j.xpro.2023.102119